Theory in Biosciences manuscript No.

(will be inserted by the editor)

Guiding the Self-organization of Random Boolean Networks

arXiv:1005.5733v2 [nlin.AO] 23 Sep 2010

Received: date / Accepted: date

Abstract Random Boolean networks (RBNs) are models of genetic regulatory networks. It is useful to describe RBNs as self-organizing systems to study how changes in the nodes and connections aect the global network dynamics. This article reviews eight dierent methods for guiding the self-organization of RBNs. In particular, the article is focussed on guiding RBNs towards the critical dynamical regime, which is near the phase transition between the ordered and dynamical phases. The properties and advantages of the critical regime for life, computation, adaptability, evolvability, and robustness are reviewed. The guidance methods of RBNs can be used for engineering systems with the features of the critical regime, as well as for studying how natural selection evolved living systems, which are also critical. Keywords guided self-organization random Boolean networks phase transitions criticality adaptability evolvability robustness

1 Self-organization and how to guide it The concept of self-organization originated within cybernetics (Ashby, 1947; von Foerster, 1960; Ashby, 1962) and has propagated into almost all scientic disciplines (Nicolis and Prigogine, 1977; Luhmann, 1995; Turcotte and Rundle, 2002; Camazine et al, 2003; Sk ar and Coveney, 2003). Given the broad domains where self-organization can be described, its formal denition is problematic (Gershenson and Heylighen, 2003; Heylighen, 2003; Gershenson, 2007; Prokopenko et al, 2009). Nevertheless, we can use the concept to study a wide variety of phenomena. To better understand self-organization, the following notion can be used: A system described as selforganizing is one in which elements interact, achieving dynamically a global function or behavior (Gershenson, 2007, p. 32). In other words, a global pattern is produced from local interactions. Examples of self-organizing systems include a cell (molecules interact to produce life), a brain (neurons interact to produce cognition), an insect colony (insects interact to perform collective tasks), ocks, schools,
This work was partially supported by SNI membership 47907 of CONACyT, M exico. Instituto de Investigaciones en Matem aticas Aplicadas y en Sistemas Universidad Nacional Aut onoma de M exico Ciudad Universitaria, A.P. 20-726 01000 M exico D.F. M exico E-mail: [email protected] http://turing.iimas.unam.mx/~cgg

herds (animals interact to coordinate collective behavior), a market (agents interact to dene prices), trac (vehicles interact to determine ow patterns), an ecosystem (species interact to achieve ecological homeostasis), a society (members interact to dene social properties such as language, culture, fashion, esthetics, ethics, and politics). In principle, almost any system can be described as self-organizing (Ashby, 1962; Gershenson and Heylighen, 2003). If a system has a set of preferred states, i.e. attractors, and we call those states organized, the system will self-organize towards them. It is useless to enter an ontological discussion on self-organization. Rather, the question is: when is it useful to describe a system as selforganizing? For example, a cell can be described as self-organizing, but also as a Boolean variable (0=dead, 1=alive). Which description is more accurate? It depends on the aim of the description (model). A model cannot be judged independently of the context where it is used. Self-organization is a useful description when at least two levels of description are present (e.g. molecules and cells, insects and colony) and we are interested in studying the relationship between the descriptions at these two levels (scales). In this way, one can describe how the interactions at the lower level aect the properties at the higher level. When only the interactions at the lower level are dened, the system can adapt to novel situations and be robust to perturbations, since the precise global behavior is not predened. Because of this, the properties of self-organizing systems can be exploited in design and engineering (Gershenson, 2007; Watson et al, 2010). The balance between self-organization and design is precisely the aim of guided self-organization (GSO) (Prokopenko, 2009). Although it is dicult to dene, GSO can be described as the steering of the selforganizing dynamics of a system towards a desired conguration. Cybernetics (Wiener, 1948; Ashby, 1956) had already a similar aim, although there was a stronger focus on control and communication, as opposed to self-organization and information. The dynamics of self-organizing systems lead them to an organized state or conguration. However, there can be several potential congurations available. The emerging study of GSO explores the constraints and conditions where self-organizing dynamics can be lead to a particular conguration. Similar to several synthetic approaches (Steels, 1993), GSO can be useful on the one hand for understanding how natural systems self-organize and on the other hand for building articial systems capable of self-organization. This paper focuses on both aspects, exploiting the generality of random Boolean networks (RBNs): First, how can evolution guide the self-organization of genetic regulatory networks? Second, how can we manipulate RBNs to guide their self-organization towards a desired regime? In the next section, random Boolean networks are briey reviewed. In Section 3 the self-organization of RBNs is described. Section 4 mentions eight dierent ways in which the self-organization of RBNs can be guided. Section 5 presents a discussion. Conclusions close the paper.

2 Random Boolean networks Random Boolean networks (RBNs) were originally proposed as models of genetic regulatory networks (Kauman, 1969, 1993). However, their generality has triggered an interest in them beyond their original purpose (Aldana-Gonz alez et al, 2003; Gershenson, 2004a). A RBN consists of N nodes linked by K connections each. Nodes are Boolean, i.e. their state is either on (1) or o (0). The state of a node at time t+1 depends on the states of its K inputs at time t by means of a Boolean function. Connections and functions are chosen randomly when the RBN is generated and remain xed during its temporal evolution. The randomly generated Boolean functions can be represented as lookup tables that represent all possible 2K combinations of input states. Fig. 1 shows an example of a part of a RBN, where every node has exactly two inputs, i.e. K = 2. Table 1 shows an arbitrary lookup table to update the state of one of the nodes. The dynamics of a RBN with N = 40, K = 2 can be seen in Fig. 2.

...

...

Fig. 1 Example of a RBN with connectivity K = 2, i.e. the state of nodes is determined by the state of two other nodes. Note that all nodes have two inputs, but not necessarily two outputs, e.g. node n aects four other nodes, while node o does not aect any other node.

Table 1 Lookup table to update node o depending on the state of nodes n and p. Lookup tables include all possible combinations of inputs, i.e. 2K rows. Dierent nodes will have dierent lookup tables, i.e. Boolean functions. n(t) 0 0 1 1 p(t) 0 1 0 1 o(t+1) 1 0 0 1

Fig. 2 Temporal evolution of a RBN with N = 40, K = 2 for a random initial state. Dark squares represent 0 and light squares represent 1. Time ows to the right, i.e. columns represent states of the network at a particular time, while a row represents the temporal evolution of the state of a node. Taken from RBNLab (Gershenson, 2005).

Since RBNs are nite (they have 2N possible states) and deterministic, eventually a state will be revisited. Then the network will have reached an attractor. The number of states in an attractor determines the period of the attractor. Point attractors have period one (a single state), while cyclic attractors have periods greater than one (multiple states, e.g. four in Fig. 2). A RBN can have one or more attractors. The set of states visited until an attractor is reached is called a transient. The set of states leading to an attractor form its basin. The basins of dierent attractors divide the state space. RBNs are dissipative, i.e. many states can ow into a single state (one state can have several predecessors), but from one state the transition is deterministic towards a single state (one state can have only one successor). The number of predecessors is also called in-degree. States without a predecessor are called Garden of Eden (GoE) states (in-degree=0), since they can only be reached from an initial condition. Fig. 3 illustrates the concepts presented above. Note the dierence between the topological network of a RBN (e.g. Fig. 1)which represents how the states of nodes aect each otherand its state network (e.g. Fig. 3)which represents the transitions of the whole state space. In the state network, each node represents a state of the network, i.e. there are 2N

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... G ... H A B C D F E

Fig. 3 Example of state transtions. B is a successor state of A and a predecessor of C . States can have many predecessors (e.g. B ), but only one successor. G is a Garden of Eden state since it has no predecessors. The attractor C D E F C has a period four.

nodes in the state network, while RBN nodes are represented in the topological network, i.e. there are N nodes in the topological network. One of the main topics of RBN research is to understand how changes in the topological network (lower scale) aect the state network (dynamics of higher scale), which is far from obvious. RBNs are a type of discrete dynamical network (Wuensche, 1998), i.e. space, time, and states are discrete. RBNs are generalizations of Boolean cellular automata (von Neumann, 1966; Wolfram, 1986, 2002), where the states of cells are determined by K neighbors, i.e. not chosen randomly, and all cells are updated using the same Boolean function (Gershenson, 2002).

3 Self-organization in random Boolean networks Random Boolean networks can be described as self-organizing systems simply because they have attractors. If we describe the attractors as organized, then the dynamics self-organize towards them (Ashby, 1962). Still, a better argument in favor of this description is that we are interested in understanding how the interactions between nodes (lower scale) aect the network dynamics and properties (higher scale). The concept of self-organization allows us to describe and relate both scales and their interactions under the same framework. The self-organization of RBNs can also be interpreted in terms of complexity reduction. For example, the human genome has approximately 25,000 genes. Thus, in principle, each cell could be in one of the 225,000 possible states of that network. This is much more than the estimated number of elementary particles arising from the Big Bang. However, there are only about 300 cell types (attractors (Kauman, 1993; Huang and Ingber, 2000)), i.e. cells self-organize towards a very limited fraction of all possible states. The main question addressed by these review paper is: in which ways can the self-organization of random Boolean networks be guided? Before presenting multiple answers to that question, it is convenient to understand the dierent dynamical behaviors that RBNs can have (Wuensche, 1998; Gershenson, 2004a). There are two dynamical phases: ordered and chaotic. The phase transition is characterized by its criticality and is also known as the edge of chaos (Kauman, 1993).

In the ordered phase, most nodes do not change their state, i.e. they are static. RBNs are robust in this phase, i.e. damage does not spread through the network, since most nodes do not change. Also, similar states tend to converge to the same attractor. On average, states have many predecessors, which leads to a high convergence (many states go to few states), short transient times, and a high density of Garden of Eden states, i.e. the percentage of all states without a predecessor is high. In the chaotic phase, most nodes are changing their state. Thus, damage spreads through chaotic networks. Therefore, RBNs are fragile in this phase. Similar states tend to diverge towards dierent attractors. On average, states have few predecessors, which leads to a low convergence, very long average transient times, and a relatively lower density of Garden of Eden states. In the critical regime, i.e. close to the transition between the ordered and chaotic phases, the extremes of both phases are balanced: some nodes change and some are static. Therefore, damage or changes can spread, but not necessarily through all of the network. Similar states tend to lie in trajectories that neither converge nor diverge in state space (Kauman, 2000, p. 171). Few nodes have many predecessors, while many nodes have few predecessors. Actually, the in-degree distribution approximates a power law (Wuensche, 1998). There is medium convergence. It has recently been found that RBNs near the critical regime maximize information storage and coherent information transfer (Lizier et al, 2008), as well as maximize Fisher information (Wang et al, 2010). It has been argued that computation and life should occur at the edge of chaos (Langton, 1990; Kauman, 1993; Crutcheld, 1994; Kauman, 2000). Even when criticality seems not to be a necessary condition for complexity (Mitchell et al, 1993), there is experimental evidence that the genetic networks of organisms from at least four kingdoms are near or within the critical regime (Balleza et al, 2008). The tendency towards criticality can be explained because of the following: On the one hand, ordered dynamics produce stability (robustness) which is desirable for preserving information (memory). However, a static system is not able to compute or adapt. On the other hand, chaotic dynamics give variability (exploration), which is necessary for computation and adaptation. Still, there is too much change within the chaotic phase to preserve information. A balance is reached in the critical regime, where the advantages of both phases can coexist: there can be enough stability and robustness to preserve information and enough variability to compute and explore. For this reason, it becomes a relevant question to ask how can we guide the self-organization of RBNs towards the critical regime. Being general models, the answers will give us information on how to achieve the same guidance within particular systems.

4 Guiding the self-organization of random Boolean networks The criticality of RBNs can depend on many dierent factors. These factors can be exploitedby engineers or by natural selectionto guide the self-organization of RBNs and similar systems towards the critical regime.

4.1 p One of the most obvious factors aecting the dynamics of a RBN is the probability p of having ones on the last column of lookup tables (Derrida and Pomeau, 1986). If p = 1, then all values in lookup tables will be one, so actually there will be no dynamics: all nodes will have a state of one after one iteration, independently on the initial state. The same case but with zero occurs for p = 0. When p = 0.5 there is the maximum variability possible in the lookup tables, i.e. no bias. As p approaches 0 or 1, RBNs tend to be more static, i.e. in the ordered regime.

4.2 K One of the most important factors determining the dynamical phase of RBNs is the connectivity K (Derrida and Pomeau, 1986; Luque and Sol e, 2000). For p = 0.5, the ordered phase is found when K < 2, the chaotic phase occurs for K > 2, while the critical regime lies at the phase transition, i.e. K = 2. As p tends towards one or zero, the phase transition moves towards greater values of K . If we focus on a single node i and calculate the probability that damaging its state (be it 0 or 1) will percolate changes through the network, then it is clear that the probability will increase with the connectivity K . We can choose a node j from one of the nodes that i can aect. There is a probability p that j will be 1, and thus a damage in i will modify j with a probability 1 p. The complementary case is the same. Now, for K nodes, we can expect that at least one change will occur if K 2p(1 p) 1 (Luque and Sol e, 1997b), i.e. chaos. Generalizing, the critical connectivity becomes (Derrida and Pomeau, 1986): 1 2p(1 p)

Kc =

(1)

4.3 Canalizing functions A canalizing function (Kauman, 1969; Stauer, 1987; Szejka and Drossel, 2007) is one in which at least one of the inputs has one value that is able to determine the value of the output of the function, regardless of the other inputs (Shmulevich and Kauman, 2004). In other words, the non-canalizing inputs of canalizing functions are not relevant. A dierent type of canalization is considered when a particular value of an input determines the output of a function, while for other(s) values of that input, the output of the function is determined by other inputs. Independently of the particular type of canalization, if there is a bias favoring canalizing functions, the phase transition will move towards greater values of K . This is possible because in practice non-canalizing inputs are cticious, i.e. removing them does not aect the state space nor the dynamics of a RBN. For more than 150 transcriptional systems, it has been found that there is a strong canalizing bias (Harris et al, 2002). Systems have K =3,4, or 5 for most cases, and few with even K =7,8, or 9 and still fall within the ordered phase. It has been shown that RBNs with nested canalizing functions have stable (ordered) dynamics, approaching criticality for low values of K (Kauman et al, 2003, 2004). Schemata can be used to describe canalization in RBNs in a concise way (Marques-Pita et al, 2008).

4.4 Silencing During normal cell life, genes can be silenced, i.e. switched o by dierent mechanisms. Silencing is also a method used for perturbing genetic regulatory networks. The RBN equivalent of silencing would be to x the value of a subset of nodes, independently on the state of their inputs. It has been shown that even chaotic networks can be forced into regular behavior when a subset of nodes is not responsive to the internal network dynamics (Luque and Sol e, 1997a). It is straightforward to assume that if a higher percentage of nodes remains xed, the dynamics will be more stable. Some studies of silencing on RBNs have been made, e.g. Serra et al (2004), although the precise relationship between silencing and criticality still remains to be studied.

4.5 Topology Until recently, RBN studies used either a homogeneous topology (K is the same for all nodes) or a normal topology (there is an average K inputs per node). This implies a uniform input distribution and no regularity in the wiring of nodes. However, the particular topology can have drastic eects on the properties of RBNs. 4.5.1 Link distribution On the one hand, topologies with more uniform rank distributions, as those used commonly, exhibit more and longer attractors, but with less correlation in their expression patterns. On the other hand, skewed topologies exhibit less and shorter attractors, but with more correlations (entropy and mutual information) (Oosawa and Savageau, 2002). A balance between these two extremes is achieved with scale-free topologies, i.e. few nodes have many inputs, while many nodes have few inputs. This advantageous balance can be used to explain why most natural networks have a scale-free topology (Aldana and Cluzel, 2003; Oikonomou and Cluzel, 2006). RBNs with a scale-free topology (Aldana, 2003) have been found to expand the advantages of the critical regime into the ordered phase, since well-connected elements can lead to the propagation of changes, i.e. adaptability even when the average connectivity would imply a static regime. It can be said that a scale-free topology expands the range of the critical regime. It has also been found that for RBNs with a scale-free distribution of outputs the average number of attractors is independent of networks size for more than three orders of magnitude (Serra et al, 2003). 4.5.2 Link regularity Classical RBNs have the same probability of linking any node to any other node, i.e. they are random networks. For the same input distributions, the opposite extreme are regular networks, i.e. where nodes are connected to their neighbors, in a cellular automata fashion. The balance between those two extremes is achieved with small-world networks (Watts and Strogatz, 1998; Bullock et al, 2010): many connections to neighbors and a few long-range connections lead to reduced average path lengths (common of random networks), while maintaining a high clustering coecient (common of regular networks) (Watts and Strogatz, 1998). In RBNs, a small world topology maximizes information transfer (Lizier et al, 2010), which is an indicator of critical dynamics.

4.6 Modularity It is well know that modularity is a prevalent property of natural systems (Callebaut and Rasskin-Gutman, 2005) and a desired feature of articial systems (Simon, 1996). Modularity is a property dicult to dene precisely, but we can agree that as system is modular if it is composed by modules, i.e. the interactions within modules are more relevant than those between modules. Modules oer a level of organization that promotes at the same time robustness and evolvability (Wagner, 2005b). On the one hand, damage within one module usually does not propagate through the whole system (robustness). On the other hand, useful changes can be exploited to nd new congurations without aecting the functionality of other modules. In the context of RBNs, initial explorations suggest that topological modules broaden the range of the critical regime towards higher connectivities (Poblanno-Balp and Gershenson, 2010), i.e. a modular structure promotes critical dynamics within the theoretical chaotic phase. This is because even with high

average connectivities, changes within one node have a low probability of propagating to other modules if there are few intermodular connections, in comparison with a non-modular network. These studies are related to topological modularity. One could argue that functional modularity is related to topological modularity (Calabretta et al, 1998), although this precise relationship remains to be studied.

4.7 Redundancy Redundancy consists of having more than one copy of an element type. Duplication combined with mutation is a usual mechanism for the creation of genes in eukaryotes (Fern andez and Sol e, 2004). When there are several copies of an element type, changes or damage can occur to one element while others continue to function. For RBNs (Gershenson et al, 2006), redundancy of links is not useful, since redundant links are ctitious inputs, i.e. they do not aect the state space. However, a redundancy of nodes prevents mutations from propagating through the network. Thus, redundant nodes increase neutrality (Kimura, 1983; van Nimwegen et al, 1999; Munteanu and Sol e, 2008), i.e. can smoothen rough landscapes. This is an advantage for robustness and for evolvability, for the same reasons as the ones discussed concerning modularity, even when redundancy is a dierent mechanism from modularity, although both can potentially be combined.

4.8 Degeneracy Degeneracyalso known as distributed robustnessis dened as the ability of elements that are structurally dierent to perform the same function or yield the same output (Edelman and Gally, 2001; Fern andez and Sol e, 2004). As modularity, it also widespread in biological systems and a promotor of robustness and evolvability. There is evidence that in genetic networks distributed robustness is equally or more important for mutational robustness (Wagner, 2005a,b) and for evolvability (Whitacre and Bender, 2010) than gene redundancy. To date, particular studies of degeneracy on RBNs are lacking. Nevertheless, it could be speculated that degeneracy should promote critical dynamics, even when this still remains to be explored.

5 Discussion In the previous section, a non-exhaustive list of factors that can be used to guide the self-organization of RBNs towards the critical regime was presented. Two categories of methods can be identied for guiding the self-organization towards criticality: moving the phase transition (with p, K , canalizing functions, or silencing) or broadening the critical regime (with balanced topologies, modularity, redundancy, or degeneracy). The rst category seems to be directed more at the node functionality and lookup tables, while the second category seems to be directed more at the connectivity between nodes. It can be speculated that natural selection can exploit these and probably other methods to guide the self-organization of genetic regulatory networks towards the critical regime. There is evidence that some of these methods are exploited by natural selection, but further studies are required to understand better the mechanisms, their constraints, how they are related, and which ones have been actually employed and to what degree by natural selection. In a similar way, engineers can guide the self-organization of RBNs and related systems using these and other methods. The purpose of designing articial systems with criticality is to provide them with the advantages of this dynamical regime, that living systems have used to survive in an unpredictable environment.

Concerning the methods that move the phase transition, if a RBN is in the ordered phase, one or several of the following can be done: Adjust p towards a value of 0.5. This will increase variety in lookup tables, and thus increase the number of nodes that change. In other words, dynamics will be promoted. Increase the connectivity K . More connections also promote richer dynamics. Decrease the number of canalizing functions (if any). Canalizing functions imply that some connections play no role on the dynamics. If these connections are changed, i.e. they become functional, dynamics will be richer. If the RBN is in the chaotic phase, complementary measures can be taken: Adjust p farther from a value of 0.5. This will increase homogeneity in lookup tables, and less nodes will be changing. This will decrease the damage sensitivity of the network, i.e. the dynamics will be less chaotic and more stable. Decrease the connectivity K . Less connections promote stability. Increase the number of canalizing functions. Canalizing functions reduce the eect of having several inputs, i.e. a high connectivity K , so changes cannot propagate as easily as with no canalizing functions. Silence some nodes by xing their state independently of their inputs. Concerning the methods that broaden the critical regime, even when they are dierent, all of them can be exploited to guide the self-organization of RBNs towards the critical regime: Promote a scale-free topology. When few nodes have many connections and most nodes have few connections, the desirable properties of the critical regime extend beyond the extremely narrow space of all possible networks that lies precisely on the phase transition (e.g. K = 2, p = 0.5). This criticality enhancement is possible because most nodes are stable, but the nodes with several connections (hubs) can trigger rich dynamics. In this way, changes can propagate through the RBN in a constrained fashion. Promote a small world topology. Having a high clustering coecient and a low average path length balances several advantages that lead to critical dynamics (Lizier et al, 2010). Promote modularity. Modules make it dicult for damage to spread through all of the network, even if the local connectivity (within a module) is high. In this way, chaotic dynamics can be constrained within modules. This prevents avalanches, where change to one node might cause drastic changes in a large part of the network. Still, modularity allows for information ow between modules. Promote redundancy. Having more than one copy of a node (or module) implies that a change on that node (or module) will not propagate through the network, since the redundant element(s) can perform the same function. Apart from smoothening rough tness landscapes (Gershenson et al, 2006), it has been noted that redundancy is a useful feature in evolvable hardware (Thompson, 1998). Promote degeneracy. The eect of degeneracy is similar to that of redundacy, but acting at a functional level. Dierent components of a system perform the same function. In certain conditions, degeneracy might be advantageous over redundancy, e.g. when a change aects all copies of the same node (or module). Nevertheless, redundancy seems to be useful for exploration via duplication and mutation. Yet another way of guiding the self-organization of RBNs towards the critical regime would be to promote certain properties as a part of the tness function of an evolutionary algorithm. For example, one could evolve critical RBNs trying to maximize input entropy variance (Wuensche, 1999), information storage, information transfer (Lizier et al, 2008), and/or Fisher information (Wang et al, 2010). Another criterion could be to try to approximate Lyapunov exponents to zero (Luque and Sol e, 2000). All of these properties characterize the critical regime. Thus, they can be used as a guidance of the evolutionary search. Nevertheless, it should be noted that guiding the self-organization of RBNs with a tness function that

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promotes criticality is not useful to explain how natural systems evolved their criticality. Still, they are a valid approach for engineering critical systems. It has been noted that the updating scheme can aect the behavior of RBNs (Harvey and Bossomaier, 1997; Gershenson, 2002). However, it does not aect the transition between the ordered and chaotic phases (Gershenson, 2004b). Still, within the chaotic phase, random mutations have less eect when the updating is non-deterministic. However, this is because basins of attraction merge with a less-deterministic updating scheme (Gershenson et al, 2003), i.e. there are less attractors. On the one hand, non-determinism reduces sensitivity to random mutations. On the other hand, non-determinism reduces the functionality of RBNs. Having this tradeo, and many dierent possible updating schemes (Giacobini et al, 2006; Darabos et al, 2009), it is dicult to argue in favor of any updating scheme in the context of this paper.

5.1 Why criticality? Some of the advantages of the critical regime were already presented, namely the balance between stability and variance that are requirements for life (Kauman, 1993, 2000) and computation (Langton, 1990; Crutcheld, 1994). In addition, the critical regime is also advantageous for adaptability, evolvability, and robustness. Adaptability can be understood as the ability of a system to produce advantageous changes in response to an environmental or internal state that will help the system to fulll its goals (Gershenson, 2007). Suppose that a system that is modelled by a RBN (such as a genetic regulatory network) is situated in an unpredictable environment. It is desirable that the system will be able to adapt to changes in the environment. Does criticality increase adaptability? Not by itself, but it is useful. An ordered RBN will not be able to adapt so easily, because most changes will have no eect on the dynamics, so there will be no response to the environmental change. A chaotic RBN will pose the opposite diculty: most changes will have a strong eect on the dynamics. Thus, it is highly probable that some of the functionality of the system will be lost. A balance is achieved by a critical RBN: changes can have an eect on the dynamics, but their propagation can be constrained, preserving most of the functionality of the system. Evolvability is the ability of random variations to sometimes produce improvement (Wagner and Altenberg, 1996). It can be seen as a particular type of adaptability, where changes occur from generation to generation. RBN evolution has already been explored (Stern, 1999; Lemke et al, 2001). For the same reasons as those exposed for adaptability, evolvability will be higher for critical RBNs. Within an evolutionary context, however, it is also important to mention the advantages of criticality to scalability (Simon, 1996), i.e. the ability to acquire novel functionalities. Since ordered RBNs have restricted dynamics and interactions, they cannot integrate novel functions too easily. Chaotic RBNs are also problematic, since novel functions most probably change the existing functionality. Critical RBNs are scalable, since novel functions can be integrated without altering existing functionalities. Intuitively, modularity promotes scalability in the most straightforward way, although other methodsi.e. critical RBNs without modularityalso allow for scalability. A system is robust if it continues to function in the face of perturbations (Wagner, 2005b; Jen, 2005). Robustness is a desirable property to complement adaptability and evolvability, since changes in the environment (perturbations) can damage or destroy a system before it can adapt or evolve. It is clear that evolution is not possible without robustness. Chaotic RBNs are not robust, since small perturbations produce drastic changes. Ordered RBNs are very robust, since they can resist most perturbations without producing changes. And when changes are produced, these do not propagate. However, ordered RBNs do not oer rich dynamics. Critical RBNs oer both advantages: rich dynamics and robustness (although not as high as the one of ordered RBNs. Note that the most robust RBNs are those without dynamics, e.g. with p = 1.).

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Topology and modularity seem to be more relevant for adaptability and evolvability, while redundancy and degeneracy seem to be more relevant for robustness. However, evolvability and robustness are interrelated properties (Yu and Miller, 2001; Ebner et al, 2002; Wagner, 2005b), both of them desirable in natural and articial systems. It has been argued by Riegler (2008) that canalization is indispensable for the evolvability of complexity. During the development of organisms, it seems that the perfect balance between adaptability and robustness changes with age, i.e. embryos are more plastic than adults (Neuman, 2008, ch. 13). Silencing seems to be a method used by organisms to tune this tradeo, although other methods might be involved in this process as well.

6 Conclusions This paper described random Boolean networks (RBNs) as self-organizing systems. Given the advantages of the critical regime of RBNs, dierent methods to guide the self-organization of RBNs towards criticality were reviewed. One can ask: which comes rst, criticality or some of the methods that promote it? Do they always come hand in hand? It seems not, since criticality can be present without canalizing functions, modularity, redundancy, degeneracy, or scale free topologies. However, these properties facilitate (guide) criticality. Therefore, there is a selective pressure in favor of these properties. Which are the pressures that have actually guided genetic regulatory networks towards criticality (Balleza et al, 2008) is an open question. Which methods of the ones presented have actually been exploited by natural selection is another open question, although there is evidence of several of them at play. Yet another open question is how are the dierent methods related. This question actually comprises a whole set of questions, relevant for networks in general, e.g. how are scale-free, small world, and modular topologies related? Is there an advantage of having combinations of them, e.g. a scale-free modular topology, over only one of them? Do Apollonian networks (Andrade et al, 2005) oer a maximal criticality? What would be theoretically the maximal criticality possible for a given family of RBNs? When is redundancy or degeneracy preferable? What are the dierences and advantages of critical RBNs produced with one or several of the presented methods? How are dierent methods related to adaptability, evolvability, and robustness? What is the proper balance between evolvability and robustness? This long list of relevant questions, which could easily continue growing, should motivate researchers to continue exploring RBNs, their self-organization, and methods for guiding it. The answers should be relevant for the scientic study of networks, articial life, and engineering.
Acknowledgements I should like to thank the guest editors of this special issue and anonymous referees for useful comments.

References Aldana M (2003) Boolean dynamics of networks with scale-free topology. Physica D 185(1):4566, URL http://dx.doi.org/10.1016/S0167-2789(03)00174-X Aldana M, Cluzel P (2003) A natural class of robust networks. Proceedings of the National Academy of Sciences of the United States of America 100(15):87108714, DOI 10.1073/pnas.1536783100, URL http://www.pnas.org/content/100/15/8710.abstract, http://www.pnas.org/content/100/15/8710. full.pdf+html

12

Aldana-Gonz alez M, Coppersmith S, Kadano LP (2003) Boolean dynamics with random couplings. In: Kaplan E, Marsden JE, Sreenivasan KR (eds) Perspectives and Problems in Nonlinear Science. A Celebratory Volume in Honor of Lawrence Sirovich, Springer Applied Mathematical Sciences Series, URL http://www.fis.unam.mx/%7Emax/PAPERS/nkreview.pdf Andrade JS, Herrmann HJ, Andrade RFS, da Silva LR (2005) Apollonian networks: Simultaneously scalefree, small world, euclidean, space lling, and with matching graphs. Phys Rev Lett 94(1):018,702, DOI 10.1103/PhysRevLett.94.018702, URL http://dx.doi.org/10.1103/PhysRevLett.94.018702 Ashby WR (1947) Principles of the self-organizing dynamic system. Journal of General Psychology 37:125 128 Ashby WR (1956) An Introduction to Cybernetics. Chapman & Hall, London, URL http://pcp.vub.ac. be/ASHBBOOK.html Ashby WR (1962) Principles of the self-organizing system. In: Foerster HV, Zopf, Jr GW (eds) Principles of Self-Organization, Pergamon, Oxford, pp 255278 Balleza E, Alvarez-Buylla ER, Chaos A, Kauman S, Shmulevich I, Aldana M (2008) Critical dynamics in genetic regulatory networks: Examples from four kingdoms. PLoS ONE 3(6):e2456, DOI 10.1371/journal. pone.0002456, URL http://dx.plos.org/10.1371%2Fjournal.pone.0002456 Bullock S, Barnett L, Di Paolo E (2010) Spatial embedding and the structure of complex networks. Complexity Early Access, DOI 10.1002/cplx.20338, URL http://dx.doi.org/10.1002/cplx.20338 Calabretta R, Nol S, Parisi D, Wagner GP (1998) Emergence of functional modularity in robots. In: Pfeifer R, Blumberg B, Meyer JA, Wilson S (eds) From Animals to Animats 5, MIT Press, pp 497504, URL http://tinyurl.com/2fubay9 Callebaut W, Rasskin-Gutman D (2005) Modularity: Understanding the Development and Evolution of Natural Complex Systems. MIT Press Camazine S, Deneubourg JL, Franks NR, Sneyd J, Theraulaz G, Bonabeau E (2003) Self-Organization in Biological Systems. Princeton University Press, URL http://www.pupress.princeton.edu/titles/ 7104.html Crutcheld J (1994) Critical computation, phase transitions, and hierarchical learning. In: Yamaguti M (ed) Towards the Harnessing of Chaos, Elsevier, Amsterdam, pp 9310 Darabos C, Giacobini M, Tomassini M (2009) Transient perturbations on scale-free Boolean networks with topology driven dynamics. In: Articial Life: Tenth European Conference on Articial Life, ECAL2009, Lecture Notes in Articial Intelligence, Springer, Budapest, Hungary Derrida B, Pomeau Y (1986) Random networks of automata: A simple annealed approximation. Europhys Lett 1(2):4549 Ebner M, Shackleton M, Shipman R (2002) How neutral networks inuence evolvability. Complexity 7(2):19 33, DOI 10.1002/cplx.10021, URL http://dx.doi.org/10.1002/cplx.10021 Edelman GM, Gally JA (2001) Degeneracy and complexity in biological systems. Proceedings of the National Academy of Sciences of the United States of America 98(24):13,76313,768, DOI 10.1073/ pnas.231499798, URL http://www.pnas.org/content/98/24/13763.abstract, http://www.pnas.org/ content/98/24/13763.full.pdf+html Fern andez P, Sol e R (2004) The role of computation in complex regulatory networks. In: Koonin EV, Wolf YI, Karev GP (eds) Power Laws, Scale-Free Networks and Genome Biology, Landes Bioscience, URL http://arxiv.org/abs/q-bio.MN/0311012 Gershenson C (2002) Classication of random Boolean networks. In: Standish RK, Bedau MA, Abbass HA (eds) Articial Life VIII: Proceedings of the Eight International Conference on Articial Life, MIT Press, pp 18, URL http://alife8.alife.org/proceedings/sub67.pdf Gershenson C (2004a) Introduction to random Boolean networks. In: Bedau M, Husbands P, Hutton T, Kumar S, Suzuki H (eds) Workshop and Tutorial Proceedings, Ninth International Conference on the Simulation and Synthesis of Living Systems (ALife IX), Boston, MA, pp 160173, URL http://uk.

13

arxiv.org/abs/nlin.AO/0408006 Gershenson C (2004b) Updating schemes in random Boolean networks: Do they really matter? In: Pollack J, Bedau M, Husbands P, Ikegami T, Watson RA (eds) Articial Life IX Proceedings of the Ninth International Conference on the Simulation and Synthesis of Living Systems, MIT Press, pp 238243, URL http://uk.arxiv.org/abs/nlin.AO/0402006 Gershenson C (2005) RBNLab. Http://rbn.sourceforge.net Gershenson C (2007) Design and Control of Self-organizing Systems. CopIt Arxives, Mexico, URL http: //tinyurl.com/DCSOS2007, http://tinyurl.com/DCSOS2007 Gershenson C, Heylighen F (2003) When can we call a system self-organizing? In: Banzhaf W, Christaller T, Dittrich P, Kim JT, Ziegler J (eds) Advances in Articial Life, 7th European Conference, ECAL 2003 LNAI 2801, Springer, Berlin, pp 606614, URL http://uk.arxiv.org/abs/nlin.AO/0303020 Gershenson C, Broekaert J, Aerts D (2003) Contextual random Boolean networks. In: Banzhaf W, Christaller T, Dittrich P, Kim JT, Ziegler J (eds) Advances in Articial Life, 7th European Conference, ECAL 2003 LNAI 2801, Springer-Verlag, pp 615624, URL http://uk.arxiv.org/abs/nlin.AO/0303021 Gershenson C, Kauman SA, Shmulevich I (2006) The role of redundancy in the robustness of random Boolean networks. In: Rocha LM, Yaeger LS, Bedau MA, Floreano D, Goldstone RL, Vespignani A (eds) Articial Life X, Proceedings of the Tenth International Conference on the Simulation and Synthesis of Living Systems., MIT Press, pp 3542, URL http://uk.arxiv.org/abs/nlin.AO/0511018 Giacobini M, Tomassini M, De Los Rios P, Pestelacci E (2006) Dynamics of scalefree semi-synchronous Boolean networks. In: Rocha LM, Yaeger LS, Bedau MA, Floreano D, Goldstone RL, Vespignani A (eds) Articial Life X, Proceedings of the Tenth International Conference on the Simulation and Synthesis of Living Systems., MIT Press, pp 17 Harris SE, Sawhill BK, Wuensche A, Kauman S (2002) A model of transcriptional regulatory networks based on biases in the observed regulation rules. Complexity 7(4):2340, DOI 10.1002/cplx.10022, URL http://dx.doi.org/10.1002/cplx.10022 Harvey I, Bossomaier T (1997) Time out of joint: Attractors in asynchronous random Boolean networks. In: Husbands P, Harvey I (eds) Proceedings of the Fourth European Conference on Articial Life (ECAL97), MIT Press, pp 6775, URL http://tinyurl.com/yxrxbp Heylighen F (2003) The science of self-organization and adaptivity. In: Kiel LD (ed) The Encyclopedia of Life Support Systems, EOLSS Publishers, Oxford, URL http://pcp.vub.ac.be/Papers/ EOLSS-Self-Organiz.pdf Huang S, Ingber DE (2000) Shape-dependent control of cell growth, dierentiation, and apoptosis: Switching between attractors in cell regulatory networks. Exp Cell Res 261:91103 Jen E (ed) (2005) Robust Design: A Repertoire of Biological, Ecological, and Engineering Case Studies. Santa Fe Institute Studies on the Sciences of Complexity, Oxford University Press, URL http://tinyurl. com/swtlz Kauman S, Peterson C, Samuelsson B, Troein C (2003) Random Boolean network models and the yeast transcriptional network. Proceedings of the National Academy of Sciences of the United States of America 100(25):14,79614,799, DOI 10.1073/pnas.2036429100, URL http://www.pnas.org/content/100/25/ 14796.abstract, http://www.pnas.org/content/100/25/14796.full.pdf+html Kauman S, Peterson C, Samuelsson B, Troein C (2004) Genetic networks with canalyzing Boolean rules are always stable. Proceedings of the National Academy of Sciences of the United States of America 101(49):17,10217,107, DOI 10.1073/pnas.0407783101, URL http://www.pnas.org/content/101/49/ 17102.abstract, http://www.pnas.org/content/101/49/17102.full.pdf+html Kauman SA (1969) Metabolic stability and epigenesis in randomly constructed genetic nets. Journal of Theoretical Biology 22:437467 Kauman SA (1993) The Origins of Order. Oxford University Press Kauman SA (2000) Investigations. Oxford University Press

14

Kimura M (1983) The Neutral Theory of Molecular Evolution. Cambridge University Press, Cambridge Langton C (1990) Computation at the edge of chaos: Phase transitions and emergent computation. Physica D 42:1237 Lemke N, Mombach JCM, Bodmann BEJ (2001) A numerical investigation of adaptation in populations of random Boolean networks. Physica A 301(14):589600, URL http://dx.doi.org/10.1016/ S0378-4371(01)00372-7 Lizier J, Prokopenko M, Zomaya A (2008) The information dynamics of phase transitions in random Boolean networks. In: Bullock S, Noble J, Watson R, Bedau MA (eds) Articial Life XI - Proceedings of the Eleventh International Conference on the Simulation and Synthesis of Living Systems, MIT Press, Cambridge, MA, USA, pp 374381, URL http://tinyurl.com/3xzx9fr Lizier J, Pritam S, Prokopenko M (2010) Information dynamics in small-world boolean networks, in Preparation Luhmann N (1995) Social Systems. Stanford University Press, URL http://tinyurl.com/28exa5f Luque B, Sol e RV (1997a) Controlling chaos in Kauman networks. Europhys Lett 37(9):597602 Luque B, Sol e RV (1997b) Phase transitions in random networks: Simple analytic determination of critical points. Physical Review E 55(1):257260, URL http://tinyurl.com/y8pk9y Luque B, Sol e RV (2000) Lyapunov exponents in random Boolean networks. Physica A 284:3345, URL http://tinyurl.com/trnd4 Marques-Pita M, Mitchell M, Rocha LM (2008) The role of conceptual structure in designing cellular automata to perform collective computation. In: Calude CS, Costa JF, Freund R, Oswald M, Rozenberg G (eds) UC, Springer, Lecture Notes in Computer Science, vol 5204, pp 146163 Mitchell M, Hraber PT, Crutcheld JP (1993) Revisiting the edge of chaos: Evolving cellular automata to perform computations. Complex Systems 7:89130, URL http://www.cs.pdx.edu/~mm/rev-edge.pdf Munteanu A, Sol e RV (2008) Neutrality and robustness in evo-devo: Emergence of lateral inhibition. PLoS Comput Biol 4(11):e1000,226, DOI 10.1371/journal.pcbi.1000226, URL http://dx.doi.org/10.1371% 2Fjournal.pcbi.1000226 Neuman Y (2008) Reviving the Living: Meaning Making in Living Systems, Studies in Multidisciplinarity, vol 6. Elsevier, Amsterdam Nicolis G, Prigogine I (1977) Self-Organization in Non-Equilibrium Systems: From Dissipative Structures to Order Through Fluctuations. Wiley van Nimwegen E, Crutcheld JP, Huynen M (1999) Neutral evolution of mutational robustness. Proceedings of the National Academy of Sciences of the United States of America 96(17):97169720, URL http://www. pnas.org/content/96/17/9716.abstract, http://www.pnas.org/content/96/17/9716.full.pdf+html Oikonomou P, Cluzel P (2006) Eects of topology on network evolution. Nature Physics 2:532536, DOI 10.1038/nphys359, URL http://dx.doi.org/10.1038/nphys359 Oosawa C, Savageau MA (2002) Eects of alternative connectivity on behavior of randomly constructed Boolean networks. Physica D 170:143161 Poblanno-Balp R, Gershenson C (2010) Modular random Boolean networks. In: Fellermann H, D orr M, Hanczyc MM, Laursen LL, Maurer S, Merkle D, Monnard PA, Sty K, Rasmussen S (eds) Articial Life XII Proceedings of the Twelfth International Conference on the Synthesis and Simulation of Living Systems, MIT Press, Odense, Denmark, pp 303304, URL http://mitpress.mit.edu/books/chapters/ 0262290758chap56.pdf Prokopenko M (2009) Guided self-organization. HFSP Journal 3(5):287289, DOI 10.2976/1.3233933, URL http://dx.doi.org/10.2976/1.3233933 Prokopenko M, Boschetti F, Ryan A (2009) An information-theoretic primer on complexity, self-organisation and emergence. Complexity 15(1):11 28, DOI 10.1002/cplx.20249, URL http://dx.doi.org/10.1002/ cplx.20249

15

Riegler A (2008) Natural or internal selection? the case of canalization in complex evolutionary systems. Articial Life 14(3):345362, DOI 10.1162/artl.2008.14.3.14308, URL http://dx.doi.org/10.1162/artl. 2008.14.3.14308, http://www.mitpressjournals.org/doi/pdf/10.1162/artl.2008.14.3.14308 Serra R, Villani M, Agostini L (2003) On the dynamics of scale-free boolean networks. In: Neural Nets, Lecture Notes in Computer Science, vol 2859, Springer Berlin / Heidelberg, pp 4349, DOI 10.1007/ 978-3-540-45216-4 4, URL http://dx.doi.org/10.1007/978-3-540-45216-4_4 Serra R, Villani M, Semeria A (2004) Genetic network models and statistical properties of gene expression data in knock-out experiments. Journal of Theoretical Biology 227(1):149157, DOI 10.1016/j.jtbi.2003. 10.018, URL http://dx.doi.org/10.1016/j.jtbi.2003.10.018 Shmulevich I, Kauman SA (2004) Activities and sensitivities in Boolean network models. Phys Rev Lett 93(4):048,701, DOI 10.1103/PhysRevLett.93.048701, URL http://dx.doi.org/10.1103/PhysRevLett. 93.048701 Simon HA (1996) The Sciences of the Articial, 3rd edn. MIT Press Sk ar J, Coveney PV (eds) (2003) Self-Organization: The Quest for the Origin and Evolution of Structure, Phil. Trans. R. Soc. Lond. A 361(1807), proceedings of the 2002 Nobel Symposium on self-organization Stauer D (1987) On forcing functions in Kaumans random Boolean networks. Journal of Statistical Physics 46(3):789794, DOI 10.1007/BF01013386, URL http://dx.doi.org/10.1007/BF01013386 Steels L (1993) Building agents out of autonomous behavior systems. In: Steels L, Brooks RA (eds) The Articial Life Route to Articial Intelligence: Building Embodied Situated Agents, Lawrence Erlbaum Stern MD (1999) Emergence of homeostasis and noise imprinting in an evolution model. PNAS 96:10,746 10,751 Szejka A, Drossel B (2007) Evolution of canalizing Boolean networks. EPJ B 56(4):373380, DOI 10.1140/ epjb/e2007-00135-2, URL http://dx.doi.org/10.1140/epjb/e2007-00135-2 Thompson A (1998) Hardware Evolution: Automatic Design of Electronic Circuits in Recongurable Hardware by Articial Evolution. Distinguished dissertation series, Springer-Verlag Turcotte DL, Rundle JB (2002) Self-organized complexity in the physical, biological, and social sciences. Proceedings of the National Academy of Sciences of the United States of America 99(Suppl 1):24632465, DOI 10.1073/pnas.012579399, URL http://dx.doi.org/10.1073/pnas.012579399 von Foerster H (1960) On self-organizing systems and their environments. In: Yovitts MC, Cameron S (eds) Self-Organizing Systems, Pergamon, New York, pp 3150 von Neumann J (1966) The Theory of Self-Reproducing Automata. University of Illinois Press, edited by A. W. Burks Wagner A (2005a) Distributed robustness versus redundancy as causes of mutational robustness. BioEssays 27(2):176188, DOI 10.1002/bies.20170, URL http://dx.doi.org/10.1002/bies.20170 Wagner A (2005b) Robustness and Evolvability in Living Systems. Princeton University Press, Princeton, NJ, URL http://www.pupress.princeton.edu/titles/8002.html Wagner G, Altenberg L (1996) Complex adaptations and the evolution of evolvability. Evolution 50(3):967 976 Wang XR, Lizier J, Prokopenko M (2010) A Fisher information study of phase transitions in random Boolean networks. In: Fellermann H, D orr M, Hanczyc MM, Laursen LL, Maurer S, Merkle D, Monnard PA, Sty K, Rasmussen S (eds) Articial Life XII Proceedings of the Twelfth International Conference on the Synthesis and Simulation of Living Systems, MIT Press, Odense, Denmark, pp 305312, URL http://tinyurl.com/37qxgtn Watson RA, Buckley CL, Mills R (2010) Optimisation in self-modelling complex adaptive systems. Complexity URL http://eprints.ecs.soton.ac.uk/21051/, accepted Watts D, Strogatz S (1998) Collective dynamics of small-worldnetworks. Nature 393(6684):440442 Whitacre JM, Bender A (2010) Degeneracy: a design principle for robustness and evolvability. Journal of Theoretical Biology 263(1):143153, DOI 10.1016/j.jtbi.2009.11.008, URL http://dx.doi.org/10.1016/

16

j.jtbi.2009.11.008 Wiener N (1948) Cybernetics; or, Control and Communication in the Animal and the Machine. Wiley and Sons, New York Wolfram S (1986) Theory and Application of Cellular Automata. World Scientic Wolfram S (2002) A New Kind of Science. Wolfram Media, URL http://www.wolframscience.com/ thebook.html Wuensche A (1998) Discrete dynamical networks and their attractor basins. In: Standish R, Henry B, Watt S, Marks R, Stocker R, Green D, Keen S, Bossomaier T (eds) Complex Systems 98, University of New South Wales, Sydney, Australia, pp 321, URL http://tinyurl.com/y6xh35 Wuensche A (1999) Classifying cellular automata automatically: Finding gliders, ltering, and relating space-time patterns, attractor basins, and the Z parameter. Complexity 4(3):4766, URL http: //tinyurl.com/y7pss7 Yu T, Miller J (2001) Neutrality and the evolvability of Boolean function landscape. In: Genetic Programming, LNCS, vol 2038, Springer, pp 204217, DOI 10.1007/3-540-45355-5 16, URL http://dx.doi.org/ 10.1007/3-540-45355-5_16